Alkylation and Dealkylation Reactions

In saturated homoisoflavanones such as eucomol (10) diazomethane in diethyl ether leads selectively to the 7-O-methyl derivative (11) (9). On addition of a more polar solvent like methanol, complete methylation to (24) is observed (9, 38). 

With dimethyl sulfate and potassium carbonate in acetone complete methylation is usually observed to give 5,7-di-O-methyleucomin (33) from eucomin (3) even at room temperature (9, 38). Using proton acceptors of appropriate basicity like sodium acetate or pivalate, only 7-O-methyleucomin (4) is formed (38). Similar results are obtained with methyl iodide and silver oxide in dimethyl formamide (9). Methylation of eucomin (3) has also been performed in benzene and 2N sodium hydroxide under controlled conditions, yielding 7-O-methyleucomin (4) together with the C-methylated derivative (54) (9). 

By treatment of 5,7-diacetoxychroman-4-one (55) with boiling dimethyl sulfate and potassium carbonate in acetone also selective methylation at C-7 takes place giving compound (56) (45). This behaviour is also observed with 7-O-acetyleucomin (49) where even room tem- 

Benzylation of eucomin (3) with benzyl bromide and potassium carbonate in dimethyl formamide gives 5,7-di-O-benzyleucomin (43). If acetone is used as solvent additional C-benzylation at C-6 or C-8 takes place (25, 24). Again sodium acetate shows complete selectivity towards the activated hydroxyl at C-7 (64). Similarly 7-0(p-bromophenacyl)euco-mol (32) is isolated from the reaction of eucomol (10) with p-bromo-phenacyl bromide and sodium acetate or pivalate in acetone (74). 

Complete dealkylation is achieved by boron tribromide in chloroform at 0° (46). Eucomin (3) and eucomol (10) are transformed to their respective demethyl derivatives (1) and (9) in good yields (64). Hydrogen 

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In an attempt to study the behavior and chemistry of coal in ionic liquids, 1,2-diphenylethane was chosen as a model compound and its reaction in acidic pyri-dinium chloroaluminate(III) melts ([PyHjCl/AlCb was investigated [69]. At 40 °C, 1,2-diphenylethane undergoes a series of alkylation and dealkylation reactions to give a mixture of products. Some of the products are shown in Scheme 5.1-40. Newman also investigated the reactions of 1,2-diphenylethane with acylating agents such as acetyl chloride or acetic anhydride in the pyridinium ionic liquid [70] and with alcohols such as isopropanol [71]. 

Alkylation and Dealkylation Reactions. Alkylation is the addition of an alkyl group to an organic compoimd. This type of reaction is commonly carried out in the presence of the Friedel-Crafits catalysts, AICI3 along with a trace of HCl. One such reaction is... 

Catalysis. An apparent characteristic of many alkylation and dealkylation reactions is their initial slowness, and it has been necessary to resort to catalysis to make the reactions proceed at a rate that will be commercially feasible. Mineral acids, such as sulfuric, phosphoric, hydrochloric, and hydrofluoric, are widely employed as are aluminum chloride, ferric chloride, boron fluoride, etc. With a wide variety of catalysts and alkylating agents to choose from, the choice of agents to use will depend on the relative costs and the reaction rates which will result. 

A broad spectrum of chemical reactions can be catalyzed by enzymes Hydrolysis, esterification, isomerization, addition and elimination, alkylation and dealkylation, halogenation and dehalogenation, and oxidation and reduction. The last reactions are catalyzed by redox enzymes, which are classified as oxidoreductases and divided into four categories according to the oxidant they utilize and the reactions they catalyze 1) dehydrogenases (reductases), 2) oxidases, 3) oxygenases (mono- and dioxygenases), and 4) peroxidases. The latter enzymes have received extensive attention in the last years as bio catalysts for synthetic applications. Peroxidases catalyze the oxidation of aromatic compounds, oxidation of heteroatom compounds, epoxidation, and the enantio-selective reduction of racemic hydroperoxides. In this article, a short overview... 

Hydrolytic cleavages, along with oxidations, reductions, alkylations, and dealkylations, constitute phase I reactions of drug metabolism. These reactions subsume all metabolic processes apt to alter drug molecules chemically and take place chiefly in the liver. In phase II (synthetic) reactions, conjugation products of either the drug itself or its phase I metabolites are formed, for instance, with glucuronic or sulfuric acid... 

In the NE reaction, lignin is degraded by boron trifluoride in the presence of excess phenol. The key step in this process is the dealkylation of DPM-type structural units formed by phenolation the Ca side chain position of the phenylpropane units. To bring this reaction sequence into clear focus, it is appropriate to discuss the alkylation and dealkylation of simple aromatic compounds. 

Under acidic conditions, the alkylation and dealkylation of aromatic compounds are reversible reactions involving several steps in which n- and CT-complexes are formed. However, dealkylation proceeds only under more drastic conditions compared with alkylation. Nevertheless, this is not always the case. For example, if the aromatic compound is of the DPM type, the dealkylation may proceed under mild conditions since the cations formed (Fig. 6.6.5) are resonance-stabilized. This statement is supported by the fact that DPM derivatives may be degraded even at room temperature by aluminum chloride to yield benzene, alkylbenzene, and alkyldiphenylmethane, together with some resinous substances (Tsuge and Tashiro 1962, 1965). 

One rather interesting aspect of the Friedel-Crafts reaction is that trialkylation of benzene often leads to a symmetrical 1,3,5-isomer rather than a 1,2,4-derivative as would be expected from the ortho-para orientation of the alkyl group introduced initially. Since alkylation by the Friedel-Crafts method has been shown to be a reversible reaction,68 this anomalous orientation has been explained on the basis that both alkylation and dealkylation occur readily in the ortho and para positions. Simultaneously, however, some alkylation occurs in the meta position but no dealkylation68 If the reaction mixture is allowed to stand in contact with aluminum chloride for some length of time, then principally meta trialkyl derivatives will be formed ... 

The rate of the alkylation or dealkylation reaction depends on the nature of both the amine and the phosphorus ester, and decreases in the order... 

Lack of isotopic exchange between organic and inorganic mercury derivatives in the Ottawa River sediments suggests that the changes in relative amounts arise from specific alkylation or dealkylation reactions. The methylation of lead ions in rivers by bacterial agency has been confirmed. ... 

Reversible nature of Friedel-Crafts alkylation of benzene derivatives has been applied to remove ortho-tert-huty group, which is an essential substituent to isolate an atropisomeric anilide derivative as a stable compound at an ambient temperature. Simpkins and coworkers reported that during the AICI3 catalyzed trans-tert-butylation reaction of the particular enamide compound (12) in benzene, enamide function undergoes Friedel-Crafts alkylation to give phenylated product (13) in good yield (Scheme 6.12) [14]. Thus, in this case, Friedel-Crafts alkylation and dealkylation occur at the same time. 

Reactions catalyzed by silica and silica-alumina surfaces (with or without added acid) closely parallel the carbonium ion reactions in homogeneous acid. The principal advantage of such acidic surfaces is that they allow alkylations and dealkylations to be conducted at temperatures in the 200 00°C region where dealkylation becomes thermodynamically favorable relative to alkylation. They are thus the catalysts of choice for cracking of petroleum distillates to branched olefins and branched alkanes. The acidic surfaces also possess the advantage of little oxidizing action. 

It is also well known that alkyl groups can be tran.sferred intramolecularly from one position to another on the same ring and intermoiccularly from one aromatic ring to another through dealkylation reactions catalyzed by Lewis acid. The intramolecular alkyl-transfer is called reorientation or isomerization and the intermolecular alkyl transfer is referred to as disproportionation. Reorientation processes arc normally faster than disproportionation. 

In conclusion, it should be mentioned that though the great majority of aromatic electrophilic substitution reactions involve displacement of hydrogen, other atoms or groups can be involved. Thus we have already seen the displacement of S03H in the reversal of sulphonation (p. 140), of alkyl in dealkylation (p. 143), and a further, less common, displacement is that of SiR3 in protodesilylation (cf. also p. 161) ... 

Trialkylstannyl chlorides undergo dealkylation in the presence of iodine chloride, as shown in reaction 27. The alkyl iodide product reacts further very slowly in the case of primary alkyl groups, however, reaction 28 proceeds readily for R = i -Pr. The mechanism involves a charge transfer complex that can be detected in the reaction mixture. The compounds involved in the process can be analysed by GC, NMR and UVV spectroscopy282. 

Transalkylation and Dealkylation. In addition to isomerizations (side-chain rearrangement and positional isomerization), transalkylation (disproportionation) [Eq. (5.56)] and dealkylation [Eq. (5.57)] are side reactions during Friedel-Crafts alkylation however, they can be brought about as significant selective hydrocarbon transformations under appropriate conditions. Transalkylation (disproportionation) is of great practical importance in the manufacture of benzene and xylenes (see Section 5.5.4) ... 

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